Cardiac iron overload promotes cardiac injury in patients with severe COVID-19

Baier, Maria J.; Wagner, Ştefan; Hupf, Julian; Evert, Katja; Evert, Matthias; Sossalla, Samuel; Jungbauer, Carsten; Maier, Lars S.; Neef, Stefan; Mustroph, Julian

doi:10.1007/s15010-021-01722-6

Cited by 14 publications

(17 citation statements)

References 10 publications

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“…In our study, respiratory failure and cardiac injury were most prevalent, followed by renal failure in patients with MOD. These findings are similar with other reports on COVID [ 19 ] and are supported by elevated troponin levels in our population of non-survivors.…”

Section: Discussionsupporting

confidence: 94%

Hyperferritinemia, Low Circulating Iron and Elevated Hepcidin May Negatively Impact Outcome in COVID-19 Patients: A Pilot Study

et al. 2022

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Inflammation in COVID-19 produces intracellular iron overload with low circulating iron available for metabolic processes. The accumulated intracellular iron generates reactive species of oxygen and results in ferroptosis, a non-programmed cell death. Since no organ is spared, iron dysmetabolism increases the mortality and morbidity. Hepcidin and the mediator interleukin 6 are believed to play a role in the process. Our aim is to evaluate the predictive values of serologic iron and inflammatory parameters in COVID-19 critically ill patients. Hence, 24 patients were included. Hepcidin and interleukin 6, along with routine blood parameters, were determined and outcomes, such as death, multiple organ damage (MOD), anemia, and need for transfusions, were assessed. The results of this pilot study indicate that iron metabolism parameters individually, as well as models consisting of multiple laboratory and clinical variables, may predict the outcomes. Further larger studies are needed to validate the results of this pilot stud. However, this paper identifies a new direction for research.

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Section: Discussionsupporting

confidence: 94%

Hyperferritinemia, Low Circulating Iron and Elevated Hepcidin May Negatively Impact Outcome in COVID-19 Patients: A Pilot Study

et al. 2022

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“…The induction of HO-1 was shown to suppress SARS-CoV-2 in vitro [7], but it is also significantly elevated in patients with severe COVID-19 (oxygen saturation level ≤95%) [8]. Strong upregulation of HO-1 suggests the involvement of both canonical and non-canonical ferroptosis pathway-mediated cell death [9]. Furthermore, SOD2 is decreased in low-density neutrophils [6], which correlates with hypercoagulation and COVID-19 severity [10].…”

Section: Introductionmentioning

confidence: 97%

Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19

Žarković

Jakovčević

Mataić

et al. 2022

Cells

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A recent comparison of clinical and inflammatory parameters, together with biomarkers of oxidative stress, in patients who died from aggressive COVID-19 and survivors suggested that the lipid peroxidation product 4-hydroxynonenal (4-HNE) might be detrimental in lethal SARS-CoV-2 infection. The current study further explores the involvement of inflammatory cells, systemic vascular stress, and 4-HNE in lethal COVID-19 using specific immunohistochemical analyses of the inflammatory cells within the vital organs obtained by autopsy of nine patients who died from aggressive SAR-CoV-2 infection. Besides 4-HNE, myeloperoxidase (MPO) and mitochondrial superoxide dismutase (SOD2) were analyzed alongside standard leukocyte biomarkers (CDs). All the immunohistochemical slides were simultaneously prepared for each analyzed biomarker. The results revealed abundant 4-HNE in the vital organs, but the primary origin of 4-HNE was sepsis-like vascular stress, not an oxidative burst of the inflammatory cells. In particular, inflammatory cells were often negative for 4-HNE, while blood vessels were always very strongly immunopositive, as was edematous tissue even in the absence of inflammatory cells. The most affected organs were the lungs with diffuse alveolar damage and the brain with edema and reactive astrocytes, whereas despite acute tubular necrosis, 4-HNE was not abundant in the kidneys, which had prominent SOD2. Although SOD2 in most cases gave strong immunohistochemical positivity similar to 4-HNE, unlike 4-HNE, it was always limited to the cells, as was MPO. Due to their differential expressions in blood vessels, inflammatory cells, and the kidneys, we think that SOD2 could, together with 4-HNE, be a potential link between a malfunctioning immune system, oxidative stress, and vascular stress in lethal COVID-19.

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“…Hyperferritinemia in patients with COVID-19 infection and the association of high ferritin levels with the severity of the illness and mortality have been investigated early in the course of the pandemic [ 38 ]. Dysregulated iron metabolism is suggested to be responsible in severe COVID-19 disease [ 38 , 39 ]. Although the exact mechanisms of ferroptosis and the association between iron are not clearly identified yet, it is well known the crucial role of iron metabolism in ferroptosis, which is a recently identified type of controlled cell death leading to excessive reactive oxygen species formation, lipid peroxidation triggered by intracellular iron accumulation, decreased iron storage capacity and glutathione depletion [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to reducing the need for myocardial biopsy, in vivo and ex vivo experiments have made significant advances in cardiac MRI, which is now considered the clinical gold standard for non-invasive detection of myocardial damage and structural changes. Researches about COVID-19 and its cardiac effects have recently focused on in vitro and ex vivo studies [ 39 , 41 ]. An in vivo study by Sharma et al [ 41 ] demonstrated that COVID-19 could infect and induce apoptosis in human induced pluripotent stem cell-derived cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

Cardiac magnetic resonance T2* mapping in patients with COVID-19 pneumonia is associated with serum ferritin level?

Özkök

Çiftçi²,

Keleş

et al. 2022

Int J Cardiovasc Imaging

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The coronavirus disease of 2019 (COVID-19)-related myocardial injury is an increasingly recognized complication and cardiac magnetic resonance imaging (MRI) has become the most commonly used non-invasive imaging technique for myocardial involvement. This study aims to assess myocardial structure by T2*-mapping which is a non-invasive gold-standard imaging tool for the assessment of cardiac iron deposition in patients with COVID-19 pneumonia without significant cardiac symptoms. Twenty-five patients with COVID-19 pneumonia and 20 healthy subjects were prospectively enrolled.Cardiac volume and function parameters, myocardial native-T1, and T2*-mapping were measured. The association of serum ferritin level and myocardial mapping was analyzed. There was no difference in terms of cardiac volume and function parameters. The T2*-mapping values were lower in patients with COVID-19 compared to controls (35.37 [IQR 31.67–41.20] ms vs. 43.98 [IQR 41.97–46.88] ms; p < 0.0001), while no significant difference was found in terms of native-T1 mapping value(p = 0.701). There was a positive correlation with T2*mapping and native-T1 mapping values (r = 0.522, p = 0.007) and negative correlation with serum ferritin values (r = − 0.653, p = 0.000), while no correlation between cardiac native-T1 mapping and serum ferritin level. Negative correlation between serum ferritin level and T2*-mapping values in COVID-19 patients may provide a non-contrast-enhanced alternative to assess tissue structural changes in patients with COVID-19. T2*-mapping may provide a non-contrast-enhanced alternative to assess tissue alterations in patients with COVID-19. Adding T2*-mapping cardiac MRI in patients with myocardial pathologies would improve the revealing of underlying mechanisms. Further in vivo and ex vivo animal or human studies designed with larger patient cohorts should be planned.

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Cardiac iron overload promotes cardiac injury in patients with severe COVID-19

Cited by 14 publications

References 10 publications

Hyperferritinemia, Low Circulating Iron and Elevated Hepcidin May Negatively Impact Outcome in COVID-19 Patients: A Pilot Study

Hyperferritinemia, Low Circulating Iron and Elevated Hepcidin May Negatively Impact Outcome in COVID-19 Patients: A Pilot Study

Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19

Cardiac magnetic resonance T2* mapping in patients with COVID-19 pneumonia is associated with serum ferritin level?

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